PROJECT SUMMARY The overall goal of this study is to improve our understanding of the neural mechanisms that underlie speech production and their breakdown in voice disorders. Our goals will be achieved through a tight coupling of computational modeling and functional magnetic resonance imaging (fMRI) studies organized around the Directions Into Velocities of Articulators (DIVA) model of speech motor control. The goal of Aim 1 is to develop a general computational framework for quantitatively comparing cognitive models with neuroimaging. Software will be developed to enable (i) the generation of whole-brain activity patterns from any model of brain function whose components are specified by a computational load function (e.g., the number of items in working memory) and a standard brain volume template location, and (ii) direct quantitative comparison between simulated brain activity and observed activity measured by a given imaging modality (e.g., fMRI, positron emission tomography, electroencephalography, and electrocorticography). DIVA and two alternative speech production models will be implemented in this framework and used to simulate whole-brain fMRI activity for a variety of speech tasks. The framework allows quantitative comparisons between models for fitting neuroimaging data, marking a significant improvement over the qualitative comparative methods that currently prevail. The goal of Aim 2 is to characterize the brain mechanisms underlying somatosensory feedback control of phonation. fMRI will be used to measure brain responses while neurotypical participants speak short sentences. On a subset of sentences, a somatosensory perturbation will be applied to the larynx. Perturbed utterances will be contrasted with unperturbed utterances to highlight the brain network responsible for counteracting the perturbation. DIVA-based hypotheses regarding this network will be tested by comparing observed brain activity to that resulting from simulations of the task using the framework developed in Aim 1. The goal of Aim 3 is to investigate somatosensory feedback control of phonation in individuals with the voice disorder adductor spasmodic dysphonia (ADSD). Prior findings suggest ADSD is due to hyper-function of the somatosensory feedback control system. This hypothesis will be tested using the larynx perturbation fMRI protocol of Aim 2 applied to individuals with ADSD. Measured brain activity from ADSD and neurologically normal participant groups will be contrasted, and computer simulations of normal and impaired versions of the DIVA model will be compared to the experimental results. Successful completion of our aims will move neuroscience from qualitative descriptions to quantitatively testable accounts of the neural processes responsible for speech and other cognitive tasks. In the longer term, the improved understanding of brain mechanisms underlying normal speech and their breakdowns in disorders such as ADSD will pave the way for improved assessment and treatment of these disorders.